Elsevier

Sleep Medicine

Volume 13, Issue 3, March 2012, Pages 252-262
Sleep Medicine

Original Article
Physiologic autonomic arousal heralds motor manifestations of seizures in nocturnal frontal lobe epilepsy: Implications for pathophysiology

https://doi.org/10.1016/j.sleep.2011.11.007Get rights and content

Abstract

Objective

This study describes changes in heart rate (HR) and HR variability (HRV) related to clinical onset of seizures in nocturnal frontal lobe epilepsy (NFLE) in order to determine whether signs of autonomic activation precede onset of seizure motor manifestations, which was selected as seizure onset (SO). Further, to clarify the nature (epileptic or physiologic) of the changes in autonomic cardiac control presumed to precede SO, time-dependent variations in HR and HRV related to physiological cortical arousals associated with motor activity (phases of transitory activation, PAT) were also investigated.

Methods

HR and HRV spectral power, quantified by means of wavelet transform, were analyzed in relation to the onset of motor manifestations in 45 NFLE seizures and 45 PAT derived from whole night video-polysomnographic recordings of ten patients and of ten control subjects, respectively.

Results

Analysis of HRV showed a shift of sympathetic/parasympathetic cardiac control toward a sympathetic predominance in the 10 s immediately preceding SO, while changes in HR were evident only one second before SO. This sympathetic activation was not associated with a sleep-wake transition or changes in respiratory activity, both of which occurred concurrently with SO. Similar changes in HR and HRV were observed in the 10 s before the motor and electroencephalographic onset of PAT.

Conclusions

Our study demonstrates that a similar autonomic activation precedes the motor manifestations of NFLE seizures and physiological arousal. This autonomic activation could represent part of the arousal response, which could be implicated in the occurrence of both seizure and arousal motor manifestations.

Introduction

Nocturnal frontal lobe epilepsy (NFLE) is characterized by a spectrum of sleep-related paroxysmal motor manifestations of variable duration and complexity [1], [2], [3], [4]. NFLE can occur either sporadically or as an autosomal dominant form (ADNFLE) [5], the latter associated with mutations in the genes encoding for subunits of the neuronal nicotinic acetylcholine receptors (nAChR) [6]. Scalp electroencephalogram (EEG) and neuroradiological investigations are usually poorly informative in NFLE [4], [7]. As a consequence, distinguishing nocturnal frontal lobe seizures (NFLS) from other sleep-related non-epileptic paroxysmal phenomena presenting with similar motor features, i.e., disorders of arousal [8], remains arduous [9], [10], [11]. A triggering role of the arousal system, which is responsible for the rhythmic oscillations of cerebral and autonomic activity during sleep, has been hypothesized for both conditions [12], [13]. An association between arousal fluctuations and NFLS has been observed [4], [14], but the time-dependent relationship between arousals and seizures, and the features of the arousal (physiological or pathological) associated with NFLS, have not been analyzed with objective methods providing both quantitative and temporal information. During sleep, the arousal response was postulated to follow a hierarchic pattern, starting with signs of autonomic activation followed by EEG changes like delta bursts and k-complexes and ending in delayed cortical activation for stimuli of greater intensity [15], [16].

However, when changes in autonomic cardiac control precede clinical seizure onset in NFLE, they could not only reflect the arousal, but also be the consequence of the epileptic discharge affecting the cerebral areas of the central autonomic network (CAN) devoted to the sympathetic and parasympathetic control of the heart [17]. Heart rate (HR) variations during NFLS have been reported [4], but their possible relationship with clinical seizure onset has not yet been analyzed, even though recordings with intracerebral electrodes clearly demonstrated that NFLS epileptic discharges could arise from regions of the CAN (prefrontal cortex, temporal lobe, and insula) involved in cardiovascular modulation [18], [19], [20].

The primary aim of our study was to describe time-dependent modifications of HR and autonomic cardiac control related to motor onset of NFLS to determine whether signs of autonomic activation precede motor manifestations of seizures.

Further, to clarify the nature (epileptic or physiologic) of autonomic changes presumed to precede clinical seizure onset, we also investigated time-dependent variations in HR and sympathetic and parasympathetic cardiac control preceding motor onset of physiological cortical arousal [21] associated with motor activity (phases of transitory activation, PAT) [22].

Autonomic cardiac control was studied through spectral analysis of HR variability (HRV) [23] by means of wavelet transform, a time-variant spectral analysis technique that has been successfully employed for time-dependent frequency analysis in several clinical conditions [24], [25], [26], [27].

Section snippets

Patients and control subjects

Patients referred to the Epilepsy and Sleep Centers of the Department of Neurological Sciences, University of Bologna for an evocative history of NFLE underwent a preliminary evaluation including full neurological examination, routine EEG during wakefulness, brain Magnetic Resonance Imaging (MRI), and a whole night video-polysomnography (VPSG). Inclusion criteria to enter the study were a clear-cut diagnosis of NFLE documented by investigations and the VPSG recording of at least two seizures

Patients

Ten patients were included in the study (six males; mean ± SEM age at VPSG = 25.3 ± 2.8 years) (Table 1). Age at seizure onset ranged from 3 to 21 years (mean ± SEM age = 10.1 ± 1.7 years). Four patients (patients 1, 3, 7, 8) had a positive family history for parasomnias and two (patients 1 and 9) for sleep talking [8]. History-taking disclosed sleep enuresis in two patients (patients 3 and 6) and febrile seizures in one (patient 1). Neurological examination and brain MRI were normal in all patients.

Discussion

This study was designed to investigate time-dependent variations in HR and sympathetic and parasympathetic cardiac control associated with NFLS, focusing on the temporal relationship between changes in autonomic cardiac control and clinical seizure onset. Since seizures in NFLE arise from sleep, the autonomic cardiac control preceding seizure motor onset is unlikely to be influenced by psychical stress or subjective symptoms like aura, but could instead be modulated by two other main factors:

Conclusions

The present study provides the first description of time-dependent variations in HR and sympathetic/parasympathetic cardiac control related to the onset of motor manifestations of NFLS. Several important conclusions emerge from the study: first, a shift of autonomic balance toward a sympathetic prevalence closely precedes NFLS motor manifestations when HR changes are not yet evident; secondly, this autonomic activation resembles that observed before physiological arousal from sleep and could

Financial support

None.

Conflict of Interest

The ICMJE Uniform Disclosure Form for Potential Conflicts of Interest associated with this article can be viewed by clicking on the following link: doi: 10.1016/j.sleep.2011.11.007.

. ICMJE Form for Disclosure of Potential Conflicts of Interest form.

Acknowledgments

We thank Professor Elio Lugaresi for his critical revision and Anne Collins for editing the manuscript.

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